SummaryUnderstanding the many-body physics of strongly correlated systems has always been a major challenge for theoretical and experimental physics. The recent advances in the field of ultracold quantum gases have opened a completely new way to study such strongly correlated systems. It is now feasible to use ultracold gases as quantum simulators for such diverse systems such as the Hubbard model or the BCS-BEC crossover. The objective of this project is to study a three-component Fermi gas in an optical lattice, a system with rich many-body physics. With our experiments we aim to contribute to the understanding of exotic phases which are discussed in the context of QCD and condensed matter physics.

Understanding the many-body physics of strongly correlated systems has always been a major challenge for theoretical and experimental physics. The recent advances in the field of ultracold quantum gases have opened a completely new way to study such strongly correlated systems. It is now feasible to use ultracold gases as quantum simulators for such diverse systems such as the Hubbard model or the BCS-BEC crossover. The objective of this project is to study a three-component Fermi gas in an optical lattice, a system with rich many-body physics. With our experiments we aim to contribute to the understanding of exotic phases which are discussed in the context of QCD and condensed matter physics.

Max ERC Funding

1 469 040 €

Duration

Start date: 2011-08-01, End date: 2016-07-31

Project acronymABYSS

ProjectABYSS - Assessment of bacterial life and matter cycling in deep-sea surface sediments

SummaryThe deep-sea floor hosts a distinct microbial biome covering 67% of the Earth’s surface, characterized by cold temperatures, permanent darkness, high pressure and food limitation. The surface sediments are dominated by bacteria, with on average a billion cells per ml. Benthic bacteria are highly relevant to the Earth’s element cycles as they remineralize most of the organic matter sinking from the productive surface ocean, and return nutrients, thereby promoting ocean primary production. What passes the bacterial filter is a relevant sink for carbon on geological time scales, influencing global oxygen and carbon budgets, and fueling the deep subsurface biosphere. Despite the relevance of deep-sea sediment bacteria to climate, geochemical cycles and ecology of the seafloor, their genetic and functional diversity, niche differentiation and biological interactions remain unknown. Our preliminary work in a global survey of deep-sea sediments enables us now to target specific genes for the quantification of abyssal bacteria. We can trace isotope-labeled elements into communities and single cells, and analyze the molecular alteration of organic matter during microbial degradation, all in context with environmental dynamics recorded at the only long-term deep-sea ecosystem observatory in the Arctic that we maintain. I propose to bridge biogeochemistry, ecology, microbiology and marine biology to develop a systematic understanding of abyssal sediment bacterial community distribution, diversity, function and interactions, by combining in situ flux studies and different visualization techniques with a wide range of molecular tools. Substantial progress is expected in understanding I) identity and function of the dominant types of indigenous benthic bacteria, II) dynamics in bacterial activity and diversity caused by variations in particle flux, III) interactions with different types and ages of organic matter, and other biological factors.

The deep-sea floor hosts a distinct microbial biome covering 67% of the Earth’s surface, characterized by cold temperatures, permanent darkness, high pressure and food limitation. The surface sediments are dominated by bacteria, with on average a billion cells per ml. Benthic bacteria are highly relevant to the Earth’s element cycles as they remineralize most of the organic matter sinking from the productive surface ocean, and return nutrients, thereby promoting ocean primary production. What passes the bacterial filter is a relevant sink for carbon on geological time scales, influencing global oxygen and carbon budgets, and fueling the deep subsurface biosphere. Despite the relevance of deep-sea sediment bacteria to climate, geochemical cycles and ecology of the seafloor, their genetic and functional diversity, niche differentiation and biological interactions remain unknown. Our preliminary work in a global survey of deep-sea sediments enables us now to target specific genes for the quantification of abyssal bacteria. We can trace isotope-labeled elements into communities and single cells, and analyze the molecular alteration of organic matter during microbial degradation, all in context with environmental dynamics recorded at the only long-term deep-sea ecosystem observatory in the Arctic that we maintain. I propose to bridge biogeochemistry, ecology, microbiology and marine biology to develop a systematic understanding of abyssal sediment bacterial community distribution, diversity, function and interactions, by combining in situ flux studies and different visualization techniques with a wide range of molecular tools. Substantial progress is expected in understanding I) identity and function of the dominant types of indigenous benthic bacteria, II) dynamics in bacterial activity and diversity caused by variations in particle flux, III) interactions with different types and ages of organic matter, and other biological factors.

Max ERC Funding

3 375 693 €

Duration

Start date: 2012-06-01, End date: 2018-05-31

Project acronymACCOMPLI

ProjectAssembly and maintenance of a co-regulated chromosomal compartment

Researcher (PI)Peter Burkhard Becker

Host Institution (HI)LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN

Call DetailsAdvanced Grant (AdG), LS2, ERC-2011-ADG_20110310

Summary"Eukaryotic nuclei are organised into functional compartments, – local microenvironments that are enriched in certain molecules or biochemical activities and therefore specify localised functional outputs. Our study seeks to unveil fundamental principles of co-regulation of genes in a chromo¬somal compartment and the preconditions for homeostasis of such a compartment in the dynamic nuclear environment.
The dosage-compensated X chromosome of male Drosophila flies satisfies the criteria for a functional com¬partment. It is rendered structurally distinct from all other chromosomes by association of a regulatory ribonucleoprotein ‘Dosage Compensation Complex’ (DCC), enrichment of histone modifications and global decondensation. As a result, most genes on the X chromosome are co-ordinately activated. Autosomal genes inserted into the X acquire X-chromosomal features and are subject to the X-specific regulation.
We seek to uncover the molecular principles that initiate, establish and maintain the dosage-compensated chromosome. We will follow the kinetics of DCC assembly and the timing of association with different types of chromosomal targets in nuclei with high spatial resolution afforded by sub-wavelength microscopy and deep sequencing of DNA binding sites. We will characterise DCC sub-complexes with respect to their roles as kinetic assembly intermediates or as representations of local, functional heterogeneity. We will evaluate the roles of a DCC- novel ubiquitin ligase activity for homeostasis.
Crucial to the recruitment of the DCC and its distribution to target genes are non-coding roX RNAs that are transcribed from the X. We will determine the secondary structure ‘signatures’ of roX RNAs in vitro and determine the binding sites of the protein subunits in vivo. By biochemical and cellular reconstitution will test the hypothesis that roX-encoded RNA aptamers orchestrate the assembly of the DCC and contribute to the exquisite targeting of the complex."

"Eukaryotic nuclei are organised into functional compartments, – local microenvironments that are enriched in certain molecules or biochemical activities and therefore specify localised functional outputs. Our study seeks to unveil fundamental principles of co-regulation of genes in a chromo¬somal compartment and the preconditions for homeostasis of such a compartment in the dynamic nuclear environment.
The dosage-compensated X chromosome of male Drosophila flies satisfies the criteria for a functional com¬partment. It is rendered structurally distinct from all other chromosomes by association of a regulatory ribonucleoprotein ‘Dosage Compensation Complex’ (DCC), enrichment of histone modifications and global decondensation. As a result, most genes on the X chromosome are co-ordinately activated. Autosomal genes inserted into the X acquire X-chromosomal features and are subject to the X-specific regulation.
We seek to uncover the molecular principles that initiate, establish and maintain the dosage-compensated chromosome. We will follow the kinetics of DCC assembly and the timing of association with different types of chromosomal targets in nuclei with high spatial resolution afforded by sub-wavelength microscopy and deep sequencing of DNA binding sites. We will characterise DCC sub-complexes with respect to their roles as kinetic assembly intermediates or as representations of local, functional heterogeneity. We will evaluate the roles of a DCC- novel ubiquitin ligase activity for homeostasis.
Crucial to the recruitment of the DCC and its distribution to target genes are non-coding roX RNAs that are transcribed from the X. We will determine the secondary structure ‘signatures’ of roX RNAs in vitro and determine the binding sites of the protein subunits in vivo. By biochemical and cellular reconstitution will test the hypothesis that roX-encoded RNA aptamers orchestrate the assembly of the DCC and contribute to the exquisite targeting of the complex."

Max ERC Funding

2 482 770 €

Duration

Start date: 2012-02-01, End date: 2017-01-31

Project acronymACCRETE

ProjectAccretion and Early Differentiation of the Earth and Terrestrial Planets

Researcher (PI)David Crowhurst Rubie

Host Institution (HI)UNIVERSITAET BAYREUTH

Call DetailsAdvanced Grant (AdG), PE10, ERC-2011-ADG_20110209

SummaryFormation of the Earth and the other terrestrial planets of our Solar System (Mercury, Venus and Mars) commenced 4.568 billion years ago and occurred on a time scale of about 100 million years. These planets grew by the process of accretion, which involved numerous collisions with smaller (Moon- to Mars-size) bodies. Impacts with such bodies released sufficient energy to cause large-scale melting and the formation of deep “magma oceans”. Such magma oceans enabled liquid metal to separate from liquid silicate, sink and accumulate to form the metallic cores of the planets. Thus core formation in terrestrial planets was a multistage process, intimately related to the major impacts during accretion, that determined the chemistry of planetary mantles. However, until now, accretion, as modelled by astrophysicists, and core formation, as modelled by geochemists, have been treated as completely independent processes. The fundamental and crucial aim of this ambitious interdisciplinary proposal is to integrate astrophysical models of planetary accretion with geochemical models of planetary differentiation together with cosmochemical constraints obtained from meteorites. The research will involve integrating new models of planetary accretion with core formation models based on the partitioning of a large number of elements between liquid metal and liquid silicate that we will determine experimentally at pressures up to about 100 gigapascals (equivalent to 2400 km deep in the Earth). By comparing our results with the known physical and chemical characteristics of the terrestrial planets, we will obtain a comprehensive understanding of how these planets formed, grew and evolved, both physically and chemically, with time. The integration of chemistry and planetary differentiation with accretion models is a new ground-breaking concept that will lead, through synergies and feedback, to major new advances in the Earth and planetary sciences.

Formation of the Earth and the other terrestrial planets of our Solar System (Mercury, Venus and Mars) commenced 4.568 billion years ago and occurred on a time scale of about 100 million years. These planets grew by the process of accretion, which involved numerous collisions with smaller (Moon- to Mars-size) bodies. Impacts with such bodies released sufficient energy to cause large-scale melting and the formation of deep “magma oceans”. Such magma oceans enabled liquid metal to separate from liquid silicate, sink and accumulate to form the metallic cores of the planets. Thus core formation in terrestrial planets was a multistage process, intimately related to the major impacts during accretion, that determined the chemistry of planetary mantles. However, until now, accretion, as modelled by astrophysicists, and core formation, as modelled by geochemists, have been treated as completely independent processes. The fundamental and crucial aim of this ambitious interdisciplinary proposal is to integrate astrophysical models of planetary accretion with geochemical models of planetary differentiation together with cosmochemical constraints obtained from meteorites. The research will involve integrating new models of planetary accretion with core formation models based on the partitioning of a large number of elements between liquid metal and liquid silicate that we will determine experimentally at pressures up to about 100 gigapascals (equivalent to 2400 km deep in the Earth). By comparing our results with the known physical and chemical characteristics of the terrestrial planets, we will obtain a comprehensive understanding of how these planets formed, grew and evolved, both physically and chemically, with time. The integration of chemistry and planetary differentiation with accretion models is a new ground-breaking concept that will lead, through synergies and feedback, to major new advances in the Earth and planetary sciences.

SummaryThe cell cortex is a highly dynamic layer of crosslinked actin filaments and myosin molecular motors beneath the cell membrane. It plays a central role in large scale rearrangements that occur inside cells. Many molecular mechanisms contribute to cortex structure and dynamics. However, cell scale physical properties of the cortex are difficult to grasp. This is problematic because for large scale rearrangements inside a cell, such as coherent flow of the cell cortex, it is the cell scale emergent properties that are important for the realization of such events. I will investigate how the actomyosin cytoskeleton behaves at a coarse grained and cellular scale, and will study how this emergent active behaviour is influenced by molecular mechanisms. We will study the cell cortex in the one cell stage C. elegans embryo, which undergoes large scale cortical flow during polarization and cytokinesis. We will combine theory and experiment. We will characterize cortex structure and dynamics with biophysical techniques such as cortical laser ablation and quantitative photobleaching experiments. We will develop and employ novel theoretical approaches to describe the cell scale mechanical behaviour in terms of an active complex fluid. We will utilize genetic approaches to understand how these emergent mechanical properties are influenced by molecular activities. A central goal is to arrive at a coarse grained description of the cortex that can predict future dynamic behaviour from the past structure, which is conceptually similar to how weather forecasting is accomplished. To date, systematic approaches to link molecular scale physical mechanisms to those on cellular scales are missing. This work will open new opportunities for cell biological and cell biophysical research, by providing a methodological approach for bridging scales, for studying emergent and large-scale active mechanical behaviours and linking them to molecular mechanisms.

The cell cortex is a highly dynamic layer of crosslinked actin filaments and myosin molecular motors beneath the cell membrane. It plays a central role in large scale rearrangements that occur inside cells. Many molecular mechanisms contribute to cortex structure and dynamics. However, cell scale physical properties of the cortex are difficult to grasp. This is problematic because for large scale rearrangements inside a cell, such as coherent flow of the cell cortex, it is the cell scale emergent properties that are important for the realization of such events. I will investigate how the actomyosin cytoskeleton behaves at a coarse grained and cellular scale, and will study how this emergent active behaviour is influenced by molecular mechanisms. We will study the cell cortex in the one cell stage C. elegans embryo, which undergoes large scale cortical flow during polarization and cytokinesis. We will combine theory and experiment. We will characterize cortex structure and dynamics with biophysical techniques such as cortical laser ablation and quantitative photobleaching experiments. We will develop and employ novel theoretical approaches to describe the cell scale mechanical behaviour in terms of an active complex fluid. We will utilize genetic approaches to understand how these emergent mechanical properties are influenced by molecular activities. A central goal is to arrive at a coarse grained description of the cortex that can predict future dynamic behaviour from the past structure, which is conceptually similar to how weather forecasting is accomplished. To date, systematic approaches to link molecular scale physical mechanisms to those on cellular scales are missing. This work will open new opportunities for cell biological and cell biophysical research, by providing a methodological approach for bridging scales, for studying emergent and large-scale active mechanical behaviours and linking them to molecular mechanisms.

Max ERC Funding

1 500 000 €

Duration

Start date: 2011-12-01, End date: 2017-08-31

Project acronymAestApp

ProjectThe Aesthetics of Applied Theatre

Researcher (PI)Matthias Warstat

Host Institution (HI)FREIE UNIVERSITAET BERLIN

Call DetailsAdvanced Grant (AdG), SH5, ERC-2011-ADG_20110406

SummaryThe project aims to systematically explore an entire field of current forms of theatre, which despite its outstanding cultural and political significance has so far largely been ignored by theatre studies. Over the past two decades, notwithstanding intense competition from television and electronic media, theatre has been able to reassert and even reinforce its relevance in many different parts of the world and in widely diverse cultural fields (politics, business, social work, development aid, health care, and education). This renewed relevance originates not in traditional, experimental, or commercial theatre but rather among the many different types of applied theatre, which set in motion constructive social processes while upholding theatre’s aesthetic claim. Theatre with clear social, political, or economic aims is experiencing an unprecedented boom. The study will analyse this cross-cultural trend against the background of new theories of the aesthetics of performances and rehearsal processes. This theatre studies approach promises precise insights into the aesthetic forms of applied theatre, which constitute the (hitherto barely researched) foundation of its political effects. It will furthermore bring to light the ethical issues of applied theatre: intense aesthetic experiences – often linked with risks when it comes to performances – do not readily fit in with the claim to restore children, youngsters, patients, and other target groups to health, integrity, and self-confidence through theatrical practice. The project aims to show how aesthetic, political, and ethical aspects interact in the practice of applied theatre. Investigations will focus on carefully selected case studies in Africa, Europe, the Middle East, and Latin America, whose comparison will make it possible for the first time to capture the worldwide landscape of applied theatre in its full diversity, but also in its overarching structures and interrelations.

The project aims to systematically explore an entire field of current forms of theatre, which despite its outstanding cultural and political significance has so far largely been ignored by theatre studies. Over the past two decades, notwithstanding intense competition from television and electronic media, theatre has been able to reassert and even reinforce its relevance in many different parts of the world and in widely diverse cultural fields (politics, business, social work, development aid, health care, and education). This renewed relevance originates not in traditional, experimental, or commercial theatre but rather among the many different types of applied theatre, which set in motion constructive social processes while upholding theatre’s aesthetic claim. Theatre with clear social, political, or economic aims is experiencing an unprecedented boom. The study will analyse this cross-cultural trend against the background of new theories of the aesthetics of performances and rehearsal processes. This theatre studies approach promises precise insights into the aesthetic forms of applied theatre, which constitute the (hitherto barely researched) foundation of its political effects. It will furthermore bring to light the ethical issues of applied theatre: intense aesthetic experiences – often linked with risks when it comes to performances – do not readily fit in with the claim to restore children, youngsters, patients, and other target groups to health, integrity, and self-confidence through theatrical practice. The project aims to show how aesthetic, political, and ethical aspects interact in the practice of applied theatre. Investigations will focus on carefully selected case studies in Africa, Europe, the Middle East, and Latin America, whose comparison will make it possible for the first time to capture the worldwide landscape of applied theatre in its full diversity, but also in its overarching structures and interrelations.

SummaryDespite improved therapy, cardiovascular diseases remain the most prevalent diseases in the European Union and the incidence is rising due to increased obesity and ageing. The fine-tuned regulation of vascular functions is essential not only for preventing atherosclerotic diseases, but also after tissue injury, where the coordinated growth and maturation of new blood vessels provides oxygen and nutrient supply. On the other hand, excessive vessel growth or the generation of immature, leaky vessels contributes to pathological angiogenesis. Thus, the regulation of the complex processes governing vessel growth and maturation has broad impacts for several diseases ranging from tumor angiogenesis, diabetic retinopathy, to ischemic cardiovascular diseases. MicroRNAs (miRs) are small noncoding RNAs, which play a crucial role in embryonic development and tissue homeostasis. However, only limited information is available regarding the role of miRs in the vasculature. MiRs regulate gene expression by binding to the target mRNA leading either to degradation or to translational repression. Because miRs control patterns of target genes, miRs represent an attractive and promising therapeutic target to interfere with complex processes such as neovascularization and repair of ischemic tissues. Therefore, the present application aims to identify miRs in the vasculature, which regulate vessel growth and vessel remodelling and may, thus, serve as therapeutic targets in ischemic diseases. Since ageing critically impairs endothelial function, neovascularization and vascular repair, we will specifically identify miRs, which are dysregulated during ageing in endothelial cells and pro-angiogenic progenitor cells, in order to develop novel strategies to rescue age-induced impairment of neovascularization. Beyond the specific scope of the present application, the principle findings may have impact for other diseases, where deregulated vessel growth causes or accelerates disease states.

Despite improved therapy, cardiovascular diseases remain the most prevalent diseases in the European Union and the incidence is rising due to increased obesity and ageing. The fine-tuned regulation of vascular functions is essential not only for preventing atherosclerotic diseases, but also after tissue injury, where the coordinated growth and maturation of new blood vessels provides oxygen and nutrient supply. On the other hand, excessive vessel growth or the generation of immature, leaky vessels contributes to pathological angiogenesis. Thus, the regulation of the complex processes governing vessel growth and maturation has broad impacts for several diseases ranging from tumor angiogenesis, diabetic retinopathy, to ischemic cardiovascular diseases. MicroRNAs (miRs) are small noncoding RNAs, which play a crucial role in embryonic development and tissue homeostasis. However, only limited information is available regarding the role of miRs in the vasculature. MiRs regulate gene expression by binding to the target mRNA leading either to degradation or to translational repression. Because miRs control patterns of target genes, miRs represent an attractive and promising therapeutic target to interfere with complex processes such as neovascularization and repair of ischemic tissues. Therefore, the present application aims to identify miRs in the vasculature, which regulate vessel growth and vessel remodelling and may, thus, serve as therapeutic targets in ischemic diseases. Since ageing critically impairs endothelial function, neovascularization and vascular repair, we will specifically identify miRs, which are dysregulated during ageing in endothelial cells and pro-angiogenic progenitor cells, in order to develop novel strategies to rescue age-induced impairment of neovascularization. Beyond the specific scope of the present application, the principle findings may have impact for other diseases, where deregulated vessel growth causes or accelerates disease states.

SummaryThe interaction of cells with the extracellular matrix or neighboring cells plays a crucial role in many cellular functions, such as motility, differentiation and controlled cell death. Expanding on pioneering studies on defined 2-D model systems, the role of the currently known determinants (geometry, topography, biochemical functionality and mechanical properties) is currently addressed in more relevant 3-D matrices. However, there is a clear lack in currently available approaches to fabricate well defined microenvironments, which are asymmetric or in which these factors can be varied independently. The central objective of ASMIDIAS is the development of a novel route to asymmetric microenvironments for cell-matrix interaction studies. Inspired by molecular self-assembly on the one hand and guided macroscale assembly on the other hand, directed assembly of highly defined microfabricated building blocks will be exploited to this end. In this modular design approach different building blocks position themselves during assembly on pre-structured surfaces to afford enclosed volumes that are restricted by the walls of the blocks. The project relies on two central elements. For the guided assembly, the balance of attractive and repulsive interactions between the building blocks (and its dependence on the object dimensions) and the structured surface shall be controlled by appropriate surface chemistry and suitable guiding structures. To afford the required functionality, new approaches to (i) topographically structure, (ii) biochemically functionalize and pattern selected sides of the microscale building blocks and (iii) to control their surface elastic properties via surface-attached polymers and hydrogels, will be developed.The resulting unique asymmetric environments will facilitate novel insight into cell-matrix interactions, which possess considerable relevance in the areas of tissue engineering, cell (de)differentiation, bacteria-surface interactions and beyond.

The interaction of cells with the extracellular matrix or neighboring cells plays a crucial role in many cellular functions, such as motility, differentiation and controlled cell death. Expanding on pioneering studies on defined 2-D model systems, the role of the currently known determinants (geometry, topography, biochemical functionality and mechanical properties) is currently addressed in more relevant 3-D matrices. However, there is a clear lack in currently available approaches to fabricate well defined microenvironments, which are asymmetric or in which these factors can be varied independently. The central objective of ASMIDIAS is the development of a novel route to asymmetric microenvironments for cell-matrix interaction studies. Inspired by molecular self-assembly on the one hand and guided macroscale assembly on the other hand, directed assembly of highly defined microfabricated building blocks will be exploited to this end. In this modular design approach different building blocks position themselves during assembly on pre-structured surfaces to afford enclosed volumes that are restricted by the walls of the blocks. The project relies on two central elements. For the guided assembly, the balance of attractive and repulsive interactions between the building blocks (and its dependence on the object dimensions) and the structured surface shall be controlled by appropriate surface chemistry and suitable guiding structures. To afford the required functionality, new approaches to (i) topographically structure, (ii) biochemically functionalize and pattern selected sides of the microscale building blocks and (iii) to control their surface elastic properties via surface-attached polymers and hydrogels, will be developed.The resulting unique asymmetric environments will facilitate novel insight into cell-matrix interactions, which possess considerable relevance in the areas of tissue engineering, cell (de)differentiation, bacteria-surface interactions and beyond.

Max ERC Funding

1 484 100 €

Duration

Start date: 2011-11-01, End date: 2016-10-31

Project acronymAUTOHEPARIN

ProjectAutomated Synthesis of Heparin and Chondroitin Libraries for the Preparation of Diverse Carbohydrate Arrays

SummaryWhile heparin, a glacosaminoglycan (GAG) has served as an anticoagulant for more than 60 years, the structure-activity relationship of heparin and chondroitin sulfate for specific interactions with proteins are still poorly understood. It has become evident that defined lengths and sequences or patterns are responsible for binding to a particular protein and modulating its biological activity. Determination of the structure-activity relationships of heparins and chondroitins creates an opportunity to modulate processes underlying viral entry, angiogenesis, kidney diseases and diseases of the central nervous system. The isolation of pure GAGs is extremely tedious and chemical synthesis is often the only means to access defined oligosaccharides. Currently available synthetic methods for the preparation of heparins and chondroitins are time consuming and lack generality. Therefore, it is still impossible to create large collections of GAG oligosaccharides for systematic studies of GAG-protein interactions. The overall goal of the project is the development of all aspects of automated GAG synthesis, the procurement of a large collection of heparin and chondroitin oligosaccharides of 2-10 sugars in length with a linker for ready attachment to microarray surfaces and other tools. These molecular tools will be employed to study the interaction of GAGs with growth factors, chemokines and other proteins. The specific aims include: 1) Synthesis of uronic acid and galactosamine building blocks; 2) Development of a new linker for automated GAG solid phase synthesis; 3) Construction of a new automated oligosaccharide synthesizer; 4) Development of methods for the automated assembly of heparin and chondroitin sulfate oligosaccharides; 5) Synthesis of a collection of defined heparin and chondroitin sulfate oligosaccharides; 6) Construction of synthetic GAG microarrays and SPR; 7) Preparation of GAG dendrimers and quantum dots.

While heparin, a glacosaminoglycan (GAG) has served as an anticoagulant for more than 60 years, the structure-activity relationship of heparin and chondroitin sulfate for specific interactions with proteins are still poorly understood. It has become evident that defined lengths and sequences or patterns are responsible for binding to a particular protein and modulating its biological activity. Determination of the structure-activity relationships of heparins and chondroitins creates an opportunity to modulate processes underlying viral entry, angiogenesis, kidney diseases and diseases of the central nervous system. The isolation of pure GAGs is extremely tedious and chemical synthesis is often the only means to access defined oligosaccharides. Currently available synthetic methods for the preparation of heparins and chondroitins are time consuming and lack generality. Therefore, it is still impossible to create large collections of GAG oligosaccharides for systematic studies of GAG-protein interactions. The overall goal of the project is the development of all aspects of automated GAG synthesis, the procurement of a large collection of heparin and chondroitin oligosaccharides of 2-10 sugars in length with a linker for ready attachment to microarray surfaces and other tools. These molecular tools will be employed to study the interaction of GAGs with growth factors, chemokines and other proteins. The specific aims include: 1) Synthesis of uronic acid and galactosamine building blocks; 2) Development of a new linker for automated GAG solid phase synthesis; 3) Construction of a new automated oligosaccharide synthesizer; 4) Development of methods for the automated assembly of heparin and chondroitin sulfate oligosaccharides; 5) Synthesis of a collection of defined heparin and chondroitin sulfate oligosaccharides; 6) Construction of synthetic GAG microarrays and SPR; 7) Preparation of GAG dendrimers and quantum dots.

Max ERC Funding

2 500 000 €

Duration

Start date: 2009-01-01, End date: 2014-12-31

Project acronymBCCI

ProjectBidirectional cortical communication interface

Researcher (PI)Wolfgang Rosenstiel

Host Institution (HI)EBERHARD KARLS UNIVERSITAET TUEBINGEN

Call DetailsAdvanced Grant (AdG), PE7, ERC-2008-AdG

SummaryThis project aims at establishing bidirectional communication via the cortical areas of the brain. In recent years there have been extensive research efforts for establishing an efferent pathway from the brain by means of cortical recordings to allow patients suffering from amyotrophic lateral sclerosis (ALS), stroke or high spinal cord lesions to interact with their environment (Birbaumer and Cohen, 2007; Wolpaw et al., 2002). As an extension this project will investigate the possibility of an afferent pathway to the brain by means of cortical stimulation, since it is ex-pected that stimulation might help to increase the information transfer rate for the efferent path-way. To achieve this there are two possible stimulation paradigms to be investigated. The first is based on the identification of optimal brain states for communication and the active maintenance of these states by stimulation. Inspired by classical conditioning, the second stimulation paradigm seeks to support and accelerate the rehabilitation process in stroke patients, as well as the learning process needed for the efferent communication pathway in ALS patients. By development of visual cortical prostheses (Schmidt et al., 1996) it became apparent that there are several fundamental problems related to cortical stimulation, which need to be solved before it is possible to evoke well-defined neural responses by stimulation - a prerequisite of the stimulation paradigms mentioned above. To overcome these problems it is envisaged to adapt stimulus parameters based on the current background brain activity by a feedback system in real time. Leveraging prior knowledge from microstimulation studies the feasibility of this approach will be evaluated by simultaneous stimulation and recording from ECoG grids and accompanied by the development of suitable algorithms.

This project aims at establishing bidirectional communication via the cortical areas of the brain. In recent years there have been extensive research efforts for establishing an efferent pathway from the brain by means of cortical recordings to allow patients suffering from amyotrophic lateral sclerosis (ALS), stroke or high spinal cord lesions to interact with their environment (Birbaumer and Cohen, 2007; Wolpaw et al., 2002). As an extension this project will investigate the possibility of an afferent pathway to the brain by means of cortical stimulation, since it is ex-pected that stimulation might help to increase the information transfer rate for the efferent path-way. To achieve this there are two possible stimulation paradigms to be investigated. The first is based on the identification of optimal brain states for communication and the active maintenance of these states by stimulation. Inspired by classical conditioning, the second stimulation paradigm seeks to support and accelerate the rehabilitation process in stroke patients, as well as the learning process needed for the efferent communication pathway in ALS patients. By development of visual cortical prostheses (Schmidt et al., 1996) it became apparent that there are several fundamental problems related to cortical stimulation, which need to be solved before it is possible to evoke well-defined neural responses by stimulation - a prerequisite of the stimulation paradigms mentioned above. To overcome these problems it is envisaged to adapt stimulus parameters based on the current background brain activity by a feedback system in real time. Leveraging prior knowledge from microstimulation studies the feasibility of this approach will be evaluated by simultaneous stimulation and recording from ECoG grids and accompanied by the development of suitable algorithms.